Evaluation of coronary function in female rats with severe type 1 diabetes: Effects of combined treatment with insulin and pyridoxamine.

BACKGROUND: This study aimed to evaluate the coronary function, myocardium, and epicardial adipose tissue (EAT) in female rats with severe type 1 diabetes and the effects of combined treatment with insulin and pyridoxamine (AGEs inhibitor). METHODS: Female Wistar rats were divided into groups: control (CTR, n = 13), type 1 diabetes (DM1, n = 12), type 1 diabetes treated with insulin (DM1 + INS, n = 11), and type 1 diabetes treated with insulin and pyridoxamine (DM1 + INS + PDX, n = 14). The vascular responsiveness was performed in the septal coronary artery and the protein expressions of AGE, RAGE, GPER, NF-kB was evaluated in the left ventricle (LV), as well as the reactive oxygen species (ROS) was measured in LV and in EAT. We analyzed plasma levels of glucose, estradiol, Nε-carboxymethylisine (CML), thiobarbituric acid reactive substances (TBARS), catalase (CAT), and superoxide dismutase (SOD). RESULTS: The maximal responses to ACh were reduced in the DM1 compared with the CTR group, accompanied by an increase in circulating glucose, CML, and TBARS. Additionally, the expression of NF-kB in LV and generation of ROS in the presence of MnTMPyP (SOD mimetic) were increased in the DM1 group compared with CTR. Only the combined treatment was effective for fully re-establish ACh relaxation response, NF-kB protein expression, ROS generation, and increased SOD activity in the DM1 + INS + PDX group. CONCLUSION: The reduction of the endothelium-dependent relaxation response in the septal coronary artery of female rats with severe type 1 diabetes was normalized with the combined treatment with insulin and pyridoxamine, associated with reduced inflammation and oxidative stress in the myocardium and increased circulating antioxidant activity.

Spleen tissue changes after restraint stress: effects of aerobic exercise training.

Inflammation has been described as a prominent mechanism involved in dysfunctions and diseases evoked by chronic stress. Notably, the spleen is an immune organ controlled by sympathetic and glucocorticoid mechanisms, but the impact of chronic stress in the spleen is not entirely understood. Besides, the impact of aerobic exercise training on the effects of chronic stress in the spleen has never been reported. Therefore, this study aimed to assess the changes caused in the spleen by repeated restraint stress and the effect of aerobic exercise training performed after a period of chronic restraint stress in rats. We identified that daily exposure to restraint stress (120 min per session, for 14 consecutive days) increased corticosterone and noradrenaline content, gene expression of glucocorticoid and ß2-adrenergic receptors, TNF-α and IL-6 levels, and increased pro-oxidant substances in the spleen. Circulating levels of corticosterone were also increased in chronically stressed animals. Exercise training (1 h a day/5 days per week, for 60 days) increased glucocorticoid receptor gene expression, interleukin (IL)-10 and antioxidant mechanisms in the spleen. Exercise also decreased splenic noradrenaline, tumoral necrosis factor (TNF)-α, and IL-6 contents. Lastly, the effects of repeated restraint stress in the spleen were mitigated in animals subjected to aerobic training. Taken together, the results reported in the present study indicate that aerobic exercise training is a relevant non-pharmacological therapeutic approach to dysfunctions in the spleen caused by a period of stress.

LAY SUMMARYDaily exposure to restraint stress increased corticosterone and noradrenaline content, gene expression of glucocorticoid and ß2-adrenergic receptors, inflammatory cytokines, and increased pro-oxidant substances in the spleen.Exercise training increased glucocorticoid receptor gene expression, interleukin (IL)-10, and antioxidant mechanisms in the spleen. Exercise also decreased splenic noradrenalin and inflammatory cytokines.The effects of repeated restraint stress in the spleen were mitigated in animals subjected to aerobic training.

Transcranial direct current stimulation modulates autonomic nervous system and reduces ambulatory blood pressure in hypertensives.

Purpose: Transcranial direct current stimulation (tDCS) seems to positively modulate the autonomic nervous system in different clinical conditions and healthy subjects; however, its effects on hypertensive (HTN) patients are not completely known. This study aimed to evaluate the effects of a tDCS or SHAM session (20 min) on blood pressure (BP) and autonomic variables of HTN patients.Materials and Methods: Subjects (n = 13) were randomly submitted to SHAM and tDCS sessions (1 week of washout). Hemodynamic and autonomic variables were measured at baseline, during, and immediately after tDCS or SHAM stimulation (Finometer®, Beatscope). Ambulatory BP measurement (ABPM) was evaluated after the experimental period.Results: Hemodynamic variables were not changed by tDCS, except for the fall in peripheral vascular resistance (Δ = -1696.51 ± 204.65 dyn.s/cm5). After the tDCS, sympathetic modulation was decreased (-61.47%), and vagal modulation was increased (+38.09%). Such acute autonomic changes may have evoked positive results observed in 24 hs-systolic blood pressure (Δ = -8.4 ± 6.2; P = .0022) and 24hs-diastolic blood pressure (Δ = -5.4 ± 4.2; P = .0010) in tDCS subjects compared with that in SHAM.Conclusion: These findings suggest that the tDCS could promote positive acute adjustments on cardiac autonomic control and reduced values on 24-hs BP of HTN patients. More than a proof-of-concept, these results may point out to the future, where brain stimulation (tDCS) can be used to HTN syndromes, such as refractory HTN.

Estrogen Deprivation and Myocardial Infarction: Role of Aerobic Exercise Training, Inflammation and Metabolomics.

In general, postmenopausal women present higher mortality, and worse prognosis after myocardial infarction (MI) compared to men, due to estrogen deficiency. After MI, cardiovascular alterations occur such as the autonomic imbalance and the pro-inflammatory cytokines increase. In this sense, therapies that aim to minimize deleterious effects caused by myocardial ischemia are important. Aerobic training has been proposed as a promising intervention in the prevention of cardiovascular diseases. On the other hand, some studies have attempted to identify potential biomarkers for cardiovascular diseases or specifically for MI. For this purpose, metabolomics has been used as a tool in the discovery of cardiovascular biomarkers. Therefore, the objective of this work is to discuss the changes involved in ovariectomy, myocardial infarction, and aerobic training, with emphasis on inflammation and metabolism.